The Drosophila Orthologue of ZBP/Vera/Vg1RBP is essential for cell migration during oogenesis

Trent P Munro1, Sunjong Kwon2, Bruce Schnapp2, Daniel St Johnston1. 1) The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom; 2) Department of Cell and Developmental Biology, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road Portland, Oregon 97201-3098, USA.

ZBP (zipcode binding protein) has previously been implicated in the localisation of β-actin mRNA to the motile edge of fibroblasts. This localisation allows for the rapid and regulated translation of actin protein at the migratory edge of the cell. We have analysed the role of the Drosophila orthologue of ZBP, known as IMP, and have shown egg chambers mutant for IMP have severe border cell migration defects. Furthermore IMP mutant embryos show a number of other phenotypes consistent with defects in cell migration.

Border cells are a specialised group of 6-8 follicle cells that delaminate as a cluster from the anterior of the egg chamber and migrate directionally between the nurse cells toward the oocyte. The events that underpin this process are similar to those that occur in metastatic neoplasms and therefore border cell migration is an attractive model system in which to study cell migration.

During migration, dynamic, actin-rich protrusions extend from the cells at the leading and trailing edge of the cluster. In IMP mutants the border cell cluster is clearly specified however the actin-rich protrusions that precede migration fail to form and the cluster remains at the anterior. We show that there is a pool of β-actin mRNA in these pre-migratory protrusions and that RNA from Actin 42A is specifically found in these cells. In addition RNA binding experiments show that the 3’UTR from Actin 42A is specifically recognised by IMP. We propose that IMP provides a key mechanism for the control of cell migration via its regulation of both the localisation and translation of β-actin mRNA.

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